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Author Crosby, M.B.; Svenson, J.L.; Zhang, J.; Nicol, C.J.; Gonzalez, F.J.; Gilkeson, G.S.
Title Peroxisome proliferation-activated receptor (PPAR)gamma is not necessary for synthetic PPARgamma agonist inhibition of inducible nitric-oxide synthase and nitric oxide Type Journal Article
Year 2005 Publication The Journal of pharmacology and experimental therapeutics Abbreviated Journal J Pharmacol Exp Ther
Volume (down) 312 Issue 1 Pages 69-76
Keywords Animals; Cell Line; Gene Expression/drug effects; Macrophages/drug effects/metabolism; Mice; Mice, Inbred C57BL; Nitric Oxide/*metabolism; Nitric Oxide Synthase/*metabolism; Nitric Oxide Synthase Type II; PPAR delta/metabolism; PPAR gamma/*agonists/deficiency; Thiazolidinediones/pharmacology
Abstract Peroxisome proliferation-activated receptor (PPAR)gamma agonists inhibit inducible nitric-oxide synthase (iNOS), tumor necrosis factor-alpha, and interleukin-6. Because of these effects, synthetic PPARgamma agonists, including thiazolidinediones, are being studied for their impact on inflammatory disease. The anti-inflammatory concentrations of synthetic PPARgamma agonists range from 10 to 50 microM, whereas their binding affinity for PPARgamma is in the nanomolar range. The specificity of synthetic PPARgamma agonists for PPARgamma at the concentrations necessary for anti-inflammatory effects is thus in question. We report that PPARgamma is not necessary for the inhibition of iNOS by synthetic PPARgamma agonists. RAW 264.7 macrophages possess little PPARgamma, yet lipopolysaccharide (LPS)/interferon (IFN)gamma-induced iNOS was inhibited by synthetic PPARgamma agonists at 20 microM. Endogenous PPARgamma was inhibited by the transfection of a dominant-negative PPARgamma construct into murine mesangial cells. In the transfected cells, synthetic PPARgamma agonists inhibited iNOS production at 10 microM, similar to nontransfected cells. Using cells from PPARgamma Cre/lox conditional knockout mice, baseline and LPS/IFNgamma-induced nitric oxide levels were higher in macrophages lacking PPARgamma versus controls. However, synthetic PPARgamma agonists inhibited iNOS at 10 microM in the PPARgamma-deficient cells, similar to macrophages from wild-type mice. These results indicate that PPARgamma is not necessary for inhibition of iNOS expression by synthetic PPARgamma agonists at concentrations over 10 microM. Intrinsic PPARgamma function, in the absence of synthetic agonists, however, may play a role in inflammatory modulation.
Address Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0022-3565 ISBN Medium
Area Expedition Conference
Notes PMID:15356214 Approved no
Call Number refbase @ user @ Serial 73
Permanent link to this record
 
 
Author Gavrilova, O.; Haluzik, M.; Matsusue, K.; Cutson, J.J.; Johnson, L.; Dietz, K.R.; Nicol, C.J.; Vinson, C.; Gonzalez, F.J.; Reitman, M.L.
Title Liver peroxisome proliferator-activated receptor gamma contributes to hepatic steatosis, triglyceride clearance, and regulation of body fat mass Type Journal Article
Year 2003 Publication The Journal of biological chemistry Abbreviated Journal J Biol Chem
Volume (down) 278 Issue 36 Pages 34268-34276
Keywords Adipose Tissue/*metabolism; Animals; Blotting, Southern; Blotting, Western; Female; Hypoglycemia/genetics; Insulin Resistance/genetics; Lipid Metabolism; Liver/*metabolism; Liver Diseases/genetics/*metabolism; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; RNA/metabolism; Receptors, Cytoplasmic and Nuclear/*genetics/*physiology; Recombination, Genetic; Thiazoles/pharmacology; *Thiazolidinediones; Time Factors; Transcription Factors/*genetics/*physiology; Triglycerides/*metabolism
Abstract Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a nuclear receptor that mediates the antidiabetic effects of thiazolidinediones. PPAR gamma is present in adipose tissue and becomes elevated in fatty livers, but the roles of specific tissues in thiazolidinedione actions are unclear. We studied the function of liver PPAR gamma in both lipoatrophic A-ZIP/F-1 (AZIP) and wild type mice. In AZIP mice, ablation of liver PPAR gamma reduced the hepatic steatosis but worsened the hyperlipidemia, triglyceride clearance, and muscle insulin resistance. Inactivation of AZIP liver PPAR gamma also abolished the hypoglycemic and hypolipidemic effects of rosiglitazone, demonstrating that, in the absence of adipose tissue, the liver is a primary and major site of thiazolidinedione action. In contrast, rosiglitazone remained effective in non-lipoatrophic mice lacking liver PPAR gamma, suggesting that adipose tissue is the major site of thiazolidinedione action in typical mice with adipose tissue. Interestingly, mice without liver PPAR gamma, but with adipose tissue, developed relative fat intolerance, increased adiposity, hyperlipidemia, and insulin resistance. Thus, liver PPAR gamma regulates triglyceride homeostasis, contributing to hepatic steatosis, but protecting other tissues from triglyceride accumulation and insulin resistance.
Address Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. oksanag@bdg10.niddk.nih.gov
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0021-9258 ISBN Medium
Area Expedition Conference
Notes PMID:12805374 Approved no
Call Number refbase @ user @ Serial 81
Permanent link to this record
 
 
Author Wells, P.G.; Bhuller, Y.; Chen, C.S.; Jeng, W.; Kasapinovic, S.; Kennedy, J.C.; Kim, P.M.; Laposa, R.R.; McCallum, G.P.; Nicol, C.J.; Parman, T.; Wiley, M.J.; Wong, A.W.
Title Molecular and biochemical mechanisms in teratogenesis involving reactive oxygen species Type Journal Article
Year 2005 Publication Toxicology and applied pharmacology Abbreviated Journal Toxicol Appl Pharmacol
Volume (down) 207 Issue 2 Suppl Pages 354-366
Keywords
Abstract Developmental pathologies may result from endogenous or xenobiotic-enhanced formation of reactive oxygen species (ROS), which oxidatively damage cellular macromolecules and/or alter signal transduction. This minireview focuses upon several model drugs (phenytoin, thalidomide, methamphetamine), environmental chemicals (benzo[a]pyrene) and gamma irradiation to examine this hypothesis in vivo and in embryo culture using mouse, rat and rabbit models. Embryonic prostaglandin H synthases (PHSs) and lipoxygenases bioactivate xenobiotics to free radical intermediates that initiate ROS formation, resulting in oxidation of proteins, lipids and DNA. Oxidative DNA damage and embryopathies are reduced in PHS knockout mice, and in mice treated with PHS inhibitors, antioxidative enzymes, antioxidants and free radical trapping agents. Thalidomide causes embryonic DNA oxidation in susceptible (rabbit) but not resistant (mouse) species. Embryopathies are increased in mutant mice deficient in the antioxidative enzyme glucose-6-phosphate dehydrogenase (G6PD), or by glutathione (GSH) depletion, or inhibition of GSH peroxidase or GSH reductase. Inducible nitric oxide synthase knockout mice are partially protected. Inhibition of Ras or NF-kB pathways reduces embryopathies, implicating ROS-mediated signal transduction. Atm and p53 knockout mice deficient in DNA damage response/repair are more susceptible to xenobiotic or radiation embryopathies, suggesting a teratological role for DNA damage, consistent with enhanced susceptibility to methamphetamine in ogg1 knockout mice with deficient repair of oxidative DNA damage. Even endogenous embryonic oxidative stress carries a risk, since untreated G6PD- or ATM-deficient mice have increased embryopathies. Thus, embryonic processes regulating the balance of ROS formation, oxidative DNA damage and repair, and ROS-mediated signal transduction may be important determinants of teratological risk.
Address Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada; Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0041-008X ISBN Medium
Area Expedition Conference
Notes PMID:16081118 Approved no
Call Number refbase @ user @ Serial 68
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Author Ahrendt, L.P.; Labouriau, R.; Malmkvist, J.; Nicol, C.J.; Christensen, J.W.
Title Development of a standard test to assess negative reinforcement learning in horses Type Journal Article
Year 2015 Publication Applied Animal Behaviour Science Abbreviated Journal Appl. Anim. Behav. Sci.
Volume (down) 169 Issue Pages 38-42
Keywords Algometry; Horse behaviour; Learning performance; Operant conditioning; Pressure-release; Horse training
Abstract Most horses are trained by negative reinforcement. Currently, however, no standardised test for evaluating horses' negative reinforcement learning ability is available. The aim of this study was to develop an objective test to investigate negative reinforcement learning in horses. Twenty-four Icelandic horses (3 years old) were included in this study. The horses were tested in a pressure-release task on three separate days with 10, 7 and 5 trials on each side, respectively. Each trial consisted of pressure being applied on the hindquarter with an algometer. The force of the pressure was increased until the horse moved laterally away from the point of pressure. There was a significant decrease in required force over trials on the first test day (P<0.001), but not the second and third day. The intercepts on days 2 and 3 differed significantly from day 1 (P<0.001), but not each other. Significantly stronger force was required on the right side compared to the left (P<0.001), but there was no difference between first and second side tested (P=0.56). Individual performance was evaluated by median-force and the change in force over trials on the first test day. These two measures may explain different characteristics of negative reinforcement learning. In conclusion, this study presents a novel, standardised test for evaluating negative reinforcement learning ability in horses.
Address
Corporate Author Thesis
Publisher Place of Publication Editor
Language Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0168-1591 ISBN Medium
Area Expedition Conference
Notes Approved no
Call Number Equine Behaviour @ team @ Serial 6650
Permanent link to this record
 
 
Author Wilkins, L.J.; Brown, S.N.; Zimmerman, P.H.; Leeb, C.; Nicol, C.J.
Title Investigation of palpation as a method for determining the prevalence of keel and furculum damage in laying hens Type Journal Article
Year 2004 Publication The Veterinary record Abbreviated Journal Vet. Rec.
Volume (down) 155 Issue 18 Pages 547-549
Keywords Animal Husbandry/methods; Animal Welfare; Animals; Bone and Bones/*injuries; Chickens/*injuries; Female; Fractures, Bone/diagnosis/epidemiology/*veterinary; Great Britain/epidemiology; Housing, Animal/standards; Oviposition; Palpation/methods/*veterinary; Poultry Diseases/*diagnosis/epidemiology; Prevalence; Sensitivity and Specificity
Abstract Old breaks of the keel and furculum were identified by palpation in 500 end-of-lay hens from 10 flocks housed in free-range and barn systems, and the results were compared with the results obtained by a full dissection and inspection. The method was considered to be sufficiently precise to be used as a diagnostic tool although people using it would need to be trained. The results obtained by dissection indicated that 50 to 78 per cent of the birds in the flocks had breaks of the furculum and keel, but no other breaks of bones were detected.
Address Department of Clinical Veterinary Science, University of Bristol, Bristol BS40 5DU
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0042-4900 ISBN Medium
Area Expedition Conference
Notes PMID:15559420 Approved no
Call Number refbase @ user @ Serial 70
Permanent link to this record
 
 
Author Nicol, C.J.; Davidson, H.P.D.; Harris, P.A.; Waters, A.J.; Wilson, A.D.
Title Study of crib-biting and gastric inflammation and ulceration in young horses Type Journal Article
Year 2002 Publication The Veterinary record Abbreviated Journal Vet. Rec.
Volume (down) 151 Issue 22 Pages 658-662
Keywords Animal Husbandry/methods; Animals; Antacids/therapeutic use; *Behavior, Animal; Diet/veterinary; Endoscopy, Gastrointestinal/veterinary; Feces/chemistry; Female; Gastritis/diet therapy/physiopathology/*veterinary; Horse Diseases/diet therapy/*physiopathology/psychology; Horses; Hydrogen-Ion Concentration; Male; Random Allocation; Stereotyped Behavior/*physiology; Stomach Ulcer/diet therapy/physiopathology/*veterinary; Treatment Outcome; Weaning
Abstract Nineteen young horses that had recently started to perform the stereotypy of crib-biting were compared with 16 non-stereotypic horses for 14 weeks. After initial observations of their behaviour and an endoscopic examination of the condition of their stomachs, the horses were randomly allocated to a control or an antacid diet At the start of the trial, the stomachs of the crib-biting foals were significantly more ulcerated and inflamed than the stomachs of the normal foals. In addition, the faecal pH of the crib-biting foals (6.05) was significantly lower than that of the normal foals (6.58). The antacid diet resulted in a significant improvement in the condition of the horses' stomachs. The crib-biting behaviour declined in most of the foals, regardless of their diet, but tended to decline to a greater extent in the foals on the antacid diet.
Address Department of Clinical Veterinary Science, University of Bristol, Langford House, Bristol BS40 5DU
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0042-4900 ISBN Medium
Area Expedition Conference
Notes PMID:12498408 Approved no
Call Number refbase @ user @ Serial 83
Permanent link to this record
 
 
Author McGreevy, P.D.; Webster, A.J.; Nicol, C.J.
Title Study of the behaviour, digestive efficiency and gut transit times of crib-biting horses Type Journal Article
Year 2001 Publication The Veterinary record Abbreviated Journal Vet. Rec.
Volume (down) 148 Issue 19 Pages 592-596
Keywords Animals; Behavior, Animal/*physiology; Case-Control Studies; *Digestion; *Gastrointestinal Motility/drug effects; Horse Diseases/*physiopathology; Horses/*physiology/psychology; Male; Stereotyped Behavior/*physiology; Sulfapyridine/blood; Sulfasalazine/diagnostic use/pharmacology
Abstract The spontaneous behaviour and the apparent digestibility of dry matter and fibre and transit times of digesta were compared in four normal horses and four crib-biters. A technique was developed for measuring total gut transit times (TGTT) by using single-stool analysis of the passage of radio-opaque polyethylene markers. Longer TGTT were recorded in the crib-biters than in the normal horses but the orocaecal transit times did not differ. The crib-biters rested less than the normal horses.
Address Department of Clinical Veterinary Science, University of Bristol, Langford
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0042-4900 ISBN Medium
Area Expedition Conference
Notes PMID:11386445 Approved no
Call Number refbase @ user @ Serial 86
Permanent link to this record
 
 
Author McGreevy, P.D.; French, N.P.; Nicol, C.J.
Title The prevalence of abnormal behaviours in dressage, eventing and endurance horses in relation to stabling Type Journal Article
Year 1995 Publication The Veterinary record Abbreviated Journal Vet. Rec.
Volume (down) 137 Issue 2 Pages 36-37
Keywords Animal Husbandry/*methods; Animals; *Behavior, Animal; Horse Diseases/*psychology; Horses; *Physical Conditioning, Animal; Prevalence; Questionnaires; *Stereotyped Behavior
Abstract The behaviour of horses competing in different disciplines was studied and the relationship between the time they spent out of the stable and the prevalence of abnormal behaviour was examined. The owners of dressage, eventing and endurance horses were sent a questionnaire and a total of 1101 responses were received, giving data on 1750 horses. The behaviours studied were wood-chewing, weaving, crib-biting/wind-sucking and box-walking. The reported percentage prevalences of abnormal behaviour for the dressage, eventing and endurance horses were 32.5, 30.8 and 19.5, respectively. The relationship between the time spent in the stable and the prevalence of abnormal behaviour was examined by chi 2 tests which showed that there were significant linear trends for the eventing group (P < 0.001) and the dressage group (P < 0.05). It is concluded that the time a horse spends out of the stable is related to the discipline for which it is being trained and in dressage and eventing horses the time spent in a stable is correlated with an increased risk of abnormal behaviour.
Address University of Bristol, Department of Clinical Veterinary Science, Langford
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0042-4900 ISBN Medium
Area Expedition Conference
Notes PMID:8525580 Approved no
Call Number refbase @ user @ Serial 89
Permanent link to this record
 
 
Author Søndergaard, E.; Jensen, M.B.; Nicol, C.J.
Title Motivation for social contact in horses measured by operant conditioning Type Journal Article
Year 2011 Publication Applied Animal Behaviour Science Abbreviated Journal Appl. Anim. Behav. Sci.
Volume (down) 132 Issue 3-4 Pages 131-137
Keywords Horse; Housing; Social behaviour; Operant conditioning; Motivation
Abstract Although horses are social animals they are often housed individually with limited social contact to other horses and this may compromise their welfare. The present study included eight young female horses and investigated the strength of motivation for access to full social contact, head contact and muzzle contact, respectively, to a familiar companion horse. Horses were housed individually next to their companion horse and separations between pens prevented physical contact. During daily test sessions horses were brought to a test area where they could access an arena allowing social contact. Arena access during 3 min was given after completion of a predetermined number of responses on a panel. Fixed ratios (FR) of 8, 16, 24, 32 and 40 responses per arena access were applied in a random order, one per daily test session, within each test week (Monday to Friday), and the number of rewards per daily test session was recorded. All horses could access all three types of social contact in a cross-over design, and an empty arena was used as control. Motivational strength was assessed using elasticity of demand functions, which were estimated based on the number of rewards earned and FR. Elasticities of demand for the three types of social contact were low (-0.20), and not significantly different, although increasing FR still resulted in a decrease in rewards obtained for all three types of social contact (P < 0.001). Across FR-levels horses earned more rewards for social contact than for an empty arena, as shown by much higher intercept values (2.51 vs. 0.99; P < 0.001). However, the elasticity of demand for infrequent access to an empty arena (-0.08) was lower than for social contact (P < 0.01) and not significantly different from zero (P = 0.07). Horses performed more social behaviour the lesser the restriction on social contact (full > head > muzzle). However, the finding that horses showed a similar and high motivation for all three types of social contact suggests that they are valued equally highly in a situation where the alternative is no social contact.
Address
Corporate Author Thesis
Publisher Place of Publication Editor
Language Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0168-1591 ISBN Medium
Area Expedition Conference
Notes Approved no
Call Number Equine Behaviour @ team @ Serial 5410
Permanent link to this record
 
 
Author Hothersall, B.; Harris, P.; Sörtoft, L.; Nicol, C.J.
Title Discrimination between conspecific odour samples in the horse (Equus caballus) Type Journal Article
Year 2010 Publication Applied Animal Behaviour Science Abbreviated Journal Appl. Anim. Behav. Sci.
Volume (down) 126 Issue 1-2 Pages 37-44
Keywords Horse; Olfaction; Social discrimination; Urine; Faeces
Abstract Behavioural observations suggest that smell is important in social discriminations between horses but balanced studies of this capacity are lacking. We used a habituation-discrimination procedure to investigate the ability of horses to distinguish between pairs of odour samples from different individuals. In Study 1, separate tests were conducted for urine, faeces or fleece fabric previously rubbed on the coat (to pick up body odour samples (BOS)) and donor pairs differed in sex, and age. 10 pregnant mares each underwent three tests, one per sample type. A test consisted of three successive 2-min presentations of a sample from Individual A with a simultaneous presentation of a sample from Individual B during the final presentation. Doubly repeated measures ANOVA indicated a main effect of sample type on investigative response (df = 2, f = 7.98, P = 0.004): durations were longer for BOS than for urine or faeces but habituation across trials was most consistent for urine. In the final presentation, mares demonstrated discrimination by investigating the novel urine sample (B) more than the repeated sample (novel: median 8.0 s, IQR = 10; repeated: median 2.5 s, IQR = 6; z = -2.558, P = 0.008). In Study 2, urine samples from castrated male donors were used and neither mares nor their 4-month-old foals discriminated between samples from different individuals in the final presentation. The findings suggest that urine odour may contain some information that horses can use to discriminate between conspecifics. This may be limited to the level of broad categories such as sex or reproductive status; further investigation is needed to reveal what functional information can be transmitted and what compounds are involved.
Address
Corporate Author Thesis
Publisher Place of Publication Editor
Language Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0168-1591 ISBN Medium
Area Expedition Conference
Notes Approved no
Call Number Equine Behaviour @ team @ Serial 5134
Permanent link to this record